The long-term goal is to investigate and determine specific factors that lead to development of endometrial cancer in postmenopausal women. Previous work supports the hypothesis that hyperinsulinemia plays a role in the development of endometrial cancer, and that the increased incidence of endometrial cancer seen in obese postmenopausal women may not only be due to increased estrogen production in the adipose tissue, but also due to the increase in the insulin levels. Specific aims of this continuing research project will be: (1) to fully characterize the nature of insulin resistance in women with endometrial cancer; (2) to perform studies on the ovarian stroma of postmenopausal women with endometrial cancer so as to investigate the mechanism by which insulin stimulates ovarian steroidogenesis; (3) to investigate the possible role of insulin on the development and progression of endometrial cancer; and (4) to investigate the role of insulin-like growth factors (IGF-I, IGF-II) in the development of endometrial cancer.These studies will provide important insight into pathogenesis of endometrial cancer and will aid in the development of preventive measures and new therapeutic approaches to improve cure rates of this cancer.